The CEHS was established in 2000 with the goal of developing a nationally competitive research program to study the mechanism of human disease and environmental impacts on human disease. In order to achieve this goal three focus areas of research were selected in order to facilitate the development of a critical mass of investigators in each area and on the basis of national need and expertise within the existing faculty. These focus areas are respiratory/immunotoxicology, neurotoxicology, and genetic and cardiovascular toxicology. With the aid of startup support five talented new faculty were hired and a sixth is being recruited. State-of-the-art core facilities were established and a strong mentoring program was put into place. This COBRE application is an ideal fit to develop the new faculty, hire additional faculty to further enhance the existing faculty and to enhance the support network and the infrastructure to develop the CEHS to a nationally competitive center. The specific aims of this application are: Aim 1 Promote the development of six talented faculty through the support of individual sub-projects Aim 2 Enhance the critical mass of competitive CEHS investigators at the UM through strategic recruitment of four new faculty. Aim 3 Establish a support network for CEHS investigators that promotes infrastructure development, collaborative interaction and facilitate mentoring. Aim 4 Enhance the infrastructure for CEHS research through the acquisition of critically needed instrumentation for a shared ICPMS and Flow Cytometer; and improve facilities, i.e., clean room for ICPMS, tissue culture, small animal surgery and a bioinformatics and computational core facility. We propose that with the achievement of these specific aims that all of the investigators supported by this COBRE grant will move into R01 funding and that the an overall research environment will have been created so that the CEHS investigators will be able to obtain a NIEHS center grant, a Ph.D. training grant from the NIEHS and program project grant support.